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Biomedical subjects

S J Cooper

Publications and source records attributed to S J Cooper.

At least 37 records · Page 2Linked to original sources
PubMed1998

Anomalies of cerebral asymmetry in schizophrenia interact with gender and age of onset: a post-mortem study.

In a post-mortem study of cerebral asymmetry in schizophrenia it was found that asymmetry of the length from the frontal pole to the central sulcus measured dorsally over the external surface of the brain on both hemispheres, showed a gender x diagnosis interaction (p = 0.002). Female controls had a left-greater-than-right asymmetry, and the male controls had a right-greater-than-left asymmetry. This pattern was reversed in schizophrenia. The converse effect was observed on a similar measure of the occipito-parietal lobes (p = 0.028). Significant changes were not seen in measures taken around the lateral surface of the hemispheres. Further, within the patient group, the frontal lobe asymmetry was related to age of onset such that leftward asymmetrical brains were associated with a later age of onset than rightward asymmetrical brains (p = 0.0463 for the females; p = 0.0162 for the males). The occipito-parietal asymmetry was not related to age of onset. We conclude that the asymmetry of the relative distribution of tissue between frontal and posterior regions of the hemispheres is altered in schizophrenia. The findings also suggest that there is an interaction between gender and cerebral asymmetry that is critical in determining age of onset.

Age of Onset↗
PubMed1998

Temporal-lobe length is reduced, and gyral folding is increased in schizophrenia: a post-mortem study.

This post-mortem study of the brains of 29 controls and 25 patients with schizophrenia investigated the length and gyral folding of the temporal lobes, and the asymmetries and inter-relationships of these two measures. The degree of gyral folding was significantly increased in schizophrenia (p = 0.002), but the orientation of the sulci was not changed (p = 0.420). Neither gender nor side affected any of the measures of gyral anatomy, nor were there any significant interactions of these variables with diagnosis. The temporal lobes were significantly shortened in schizophrenia, on two different measures (p = 0.009, and p = 0.001), and on one of these, females had shorter temporal lobes than males (p < 0.0005). No diagnosis x side interactions were found. The temporal-lobe shortening remained after controlling for brain weight and was not statistically related to gyral folding. These two structural changes may reflect an alteration of the cortico-cortical connectivity of the brain in schizophrenia.

Aged↗
PubMed1998

Plasma norepinephrine response to a cold pressor test in subtypes of depressive illness.

Noradrenergic systems have been shown to be disordered in depressive illness. The plasma norepinephrine response to a cold pressor test was used to investigate norepinephrine activity in subtypes of depressive illness. Patients with melancholic or psychotic depression, non-melancholic depression, general anxiety disorder and normal control subjects had a cold pressor test carried out under standard conditions. Blood samples were taken to measure plasma norepinephrine during the test. The plasma norepinephrine response to a cold pressor test was reduced in the melancholic/psychotic depressed patients compared to control subjects. No other intergroup comparisons were statistically significant. These results suggest noradrenergic systems are disturbed and subresponsive to stress in melancholic/psychotic depressed patients. This does not appear related to other clinical or biochemical factors.

Adult↗
PubMed1998

Central 5-HT3 receptors in P and in AA alcohol-preferring rats: An autoradiographic study.

Considerable evidence exists for an involvement of serotonergic mechanisms in the control of alcohol consumption. In the present study, an extensive 5-hydroxytryptamine (5-HT3) receptor autoradiographical investigation was performed using two genetically selected rat strains, alcohol preferring (P) and Alko alcohol (AA) alcohol-preferring rats, as well as the corresponding alcohol nonpreferring (NP) and Alko nonalcohol (ANA) alcohol-nonpreferring rats. The aim was to determine if there are any differences in 5-HT3 binding levels that may illuminate mechanisms of alcohol preference in these animals. For quantitating 5-HT3 binding sites, [3H]S(-)zacopride (0.5 nM) was used. Non-specific binding was measured in the presence of granisetron 10(-6) M. The [3H]S(-)zacopride binding density was measured in two subregions of the amygdaloid nucleus, frontal cortex, piriform cortex, cingulate laminae, parietal anterior cortex, parietal medial cortex, hippocampus CA1, hippocampus CA3, and entorhinal cortex. In all the brain areas investigated, the results showed no differences between AA and ANA rats. In P rats, compared to NP controls, there was a 30% lower 5-HT3 binding level in the lateral nucleus and the posteromedial cortical nucleus of the amygdala. These findings suggest that the expression of high alcohol preference in genetically selected P and AA rats is not associated with a general alteration of central 5-HT3 receptors, although a lower 5-HT3 receptor level in the amygdala of P rats may contribute to the phenotype of this strain of animals.

Alcohol Drinking↗
PubMed1998

Evidence for early opioid modulation of licking responses to sucrose and intralipid: a microstructural analysis in the rat.

The behavioural mechanisms underlying the effects of the opioid antagonist naloxone (0.3-3 mg/kg i.p.), and the opioid agonists morphine (0.3-3 mg/kg s.c.), and U-50, 488H (0.3-3 mg/kg s.c.) on ingestive behaviour were investigated using a microstructural analysis of licking patterns for sucrose solutions and Intralipid (fat emulsions) in a brief contact test. Naloxone dose-dependently decreased the total number of licks and the number of bouts for sucrose and Intralipid, but did not affect mean bout duration. Morphine dose-dependently increased the total number of licks and the number of bouts for both test fluids. For Intralipid but not for sucrose drinking, morphine actually decreased mean bout duration. U-50, 488H significantly affected total licks, although the dose-effect relationship showed an inverted U-shaped function. There was a dose-dependent increase in mean bout duration following administration of U-50, 488H and an increase in bout number, although only the lowest dose differed significantly from the control condition. The results show that microstructural analysis can distinguish between the effects of naloxone, morphine and U-50, 488H on licking behaviour and indicate that selective opioid receptor subtypes may be differentially involved in ingestive processes.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1998

Antineophobic effect of the neuroactive steroid 3alpha-hydroxy-5beta-pregnan-20-one in male rats.

The neuroactive steroid 3alpha-hydroxy-5beta-pregnan-20-one (pregnanolone) and benzodiazepine receptor (BZR) agonists share sedative, anxiolytic, and anticonvulsant properties. Recent evidence suggests that like BZR agonists, pregnanolone may also modulate feeding responses. The present experiments examined the behavioral mechanisms responsible for any hyperphagic effect of pregnanolone. The effect of pregnanolone (1-10 mg/kg i.p.) on the intake and microstructure of licking for two sucrose solutions (1 and 3%) in well familiarized nondeprived male rats under either light or dark conditions was examined. Pregnanolone had no effect on either intake or the duration or number of bouts of licking in these experiments, although in all cases the intrabout lick rate was significantly reduced at the highest dose. Pregnanolone (1-10 mg/kg) also failed to increase intake of a sweet wet mash in familiarized nondeprived male rats. However, in a food choice test where both novel and familiar food items were available, pregnanolone (1-3 mg/kg) significantly increased the time spent eating the novel food. These results suggest that unlike BZR agonists, which enhance feeding responses directly, pregnanolone may facilitate feeding secondarily via an attenuation of anxiety.

Animals↗
PubMed1998

Effect of local sequence inversions on the crystalline antiparallel beta-sheet lamellar structures of periodic polypeptides: implications for chain-folding.

The crystal structure and texture of the monodisperse periodic polypeptide [(AG)3EG(GA)3EG]10 (poly(+/-AG)3EG: A=alanine, G=glycine, E=glutamic acid) were analyzed by X-ray diffraction, Fourier transform infrared spectroscopy, and electron microscopy. Structure determination was aided by comparison with the recently described structure for the related periodic polypeptide [(AG)3EG]36 by Krejchi et al. (Macromolecules 1997;30:5012). Texture-oriented samples of poly(+/-AG)3EG were obtained by crystallization of the polymer from aqueous formic acid solution. The evidence supports an antiparallel (ap) beta-sheet protein structure and the X-ray diffraction signals index on an orthorhombic unit cell with parameters: a=0.950 nm (hydrogen-bond direction), b=1.052 nm (apbeta-sheet stacking direction), c=6.95 nm (chain direction). The absence of the (010) diffraction signal, a prominent signal in the poly(AG)3EG diffraction pattern, implies that the apbeta-sheets are 'apolar', i.e. both surfaces are equally populated with alanyl methyl groups. Selective line broadening of wide-angle diffraction signals with l not equal to 0 gives an estimated crystal size of approximately/= 4 nm in the chain direction. This observation, coupled with the appearance of low-angle particle interference peaks, indicates a crystal thickness considerably less than the chain length and suggests an adjacent-re-entry chain-folded lamellar structure incorporating the apbeta-sheet architecture. The polypeptide folds through gamma-turns, in-phase with the pseudo-octapeptide repeat; the glutamic acid residues occur on the lamellar surfaces. These results and those from the crystalline lamellae of poly(AG)3EG suggest that beta-turns are not compatible with these repetitively stacked apbeta-sheet structures. This implies that intersheet interactions of alanyl methyl groups and glycyl alpha-protons are not sufficiently strong to dictate the folding geometry in these structures.

Crystallization↗
PubMed1998

Effects of benzodiazepine receptor ligands on the ingestion of sucrose, intralipid, and maltodextrin: an investigation using a microstructural analysis of licking behavior in a brief contact test.

Microstructural analysis of licking behavior in the rat was conducted (a) to describe in detail the characteristics of benzodiazepine-induced changes in ingestion and (b) to determine if the changes are consistent with an alteration in palatability. The effects of the benzodiazepine receptor (BZR) agonist midazolam (0.3-3 mg/kg), and the partial inverse agonist Ro 15-4513 (0.3-3 mg/kg), on licking for several concentrations of sucrose, Intralipid, and maltodextrin in a brief contact test were investigated. Midazolam increased the total number of licks for all 3 fluids; conversely, Ro 15-4513 decreased the total number of licks. Midazolam increased mean bout duration for sucrose and maltodextrin drinking and there was a trend toward a similar effect with Intralipid drinking. Ro 15-4513 reduced mean bout duration for all 3 test fluids. These data are discussed in terms of bidirectional changes in fluid palatability by drug actions at BZRs.

Analysis of Variance↗
PubMed1998

Differences and variability in plasma noradrenaline between depressive and anxiety disorders.

Plasma noradrenaline (NA) levels were compared between two groups of patients with major depressive disorder (melancholic/psychotic and non-melancholic), patients with general anxiety disorders and healthy controls. The melancholic/psychotic depressed group had the highest plasma NA levels. This only reached statistical significance with respect to the control group. Within the depressed group, there was no association between plasma NA levels and age, weight loss, ratings of depression, anxiety or plasma cortisol levels. Variance of plasma NA was greatest in the melancholic/psychotic depressed group. A review of previous studies shows an association between raised plasma NA, depressive illness and alterations in NA variance. This association may be limited to melancholic/psychotic depressed patients. The above findings support a dysregulated noradrenergic system in depressive illness.

Adult↗
PubMed1997

Prospective study of biofeedback for treatment of constipation.

PURPOSE: This study was designed to evaluate prospectively the results of pelvic floor physiotherapy with the aid of biofeedback in a heterogeneous group of patients with intractable constipation. METHODS: Biofeedback was used to treat 19 patients (age range, 16-78 (median, 63) years) with intractable constipation. Assessment, using visual linear analog scales of symptoms, was performed prospectively by an independent researcher. Biofeedback was performed by a physiotherapist, and patients were required to attend six sessions on an outpatient basis. The cause of constipation was heterogeneous, with no specific disorder being implicated on testing with anal manometry, defecating proctography, and colonic transit time. RESULTS: At six weeks, there was a median 27 percent (range, -8-93 percent) improvement in symptom scores. At six months, there was a median 23 percent (range, -54-64 percent) improvement in symptom scores. These were statistically significant compared with the scores at outset, six weeks (P = 0.0006), and six months (P = 0.012). However, only two (12.5 percent) patients at the six-month follow-up had an improvement of greater than 50 percent in their symptoms. CONCLUSION: Biofeedback is not recommended in the management of constipation.

Adolescent↗
PubMed1997

Prospective trial of pelvic floor retraining in patients with fecal incontinence.

PURPOSE: Our aim was to prospectively evaluate pelvic floor retraining (PFR) in improving symptomatic fecal incontinence. METHODS: PFR was used to treat 30 patients with fecal incontinence (28 women; age range, 29-85 (median, 68) years). PFR was performed by a physiotherapist in the outpatient department according to a strict protocol and included biofeedback using an anal plug electromyometer. Manometry (24 patients), pudendal nerve terminal motor latency (PNTML, 16 patients), and anal ultrasound (14 patients) were done before commencing therapy. Independent assessment of symptoms was done at the commencement of therapy, at 6 weeks, and at 6 and 12 months posttherapy. RESULTS: Twenty patients (67 percent) had improved incontinence scores, with eight patients (27 percent) being completely or nearly free of symptoms. Of 28 patients followed up longer than six months, 14 achieved a 25 percent or greater improvement at six weeks, which was sustained in all cases. Fourteen had an initial improvement of less than 25 percent, with only four (29 percent) showing later improvement (P < 0.0001). There was no relationship between results of the therapy and patient age, initial severity of symptoms, etiology of incontinence, and results of anal manometry, PNTML, and anal ultrasound. CONCLUSIONS: PFR is a physical therapy that should be considered as the initial treatment in patients with fecal incontinence. An improvement can be expected in up to 67 percent of patients. Initial good results can predict overall outcome.

Adult↗
PubMed1997

Midazolam-induced rapid changes in licking behaviour: evidence for involvement of endogenous opioid peptides.

The role of endogenous opioid peptides in the effects of midazolam on ingestive behaviour was investigated using a detailed analysis of licking behaviour in the rat. Midazolam (1.8 mg/kg i.p.) was administered in combination with either flumazenil (10 and 20 mg/kg i.p.) or naloxone (0.1 and 0.3 mg/kg i.p.). The effect on licking patterns during 60-s exposures to a range of concentrations of a fat emulsion (Intralipid) was then recorded. Midazolam significantly increased the total number of licks for Intralipid by increasing the mean bout duration. This effect is consistent with the proposal that benzodiazepines enhance palatability. Flumazenil and naloxone were ineffective when administered alone, but both drugs blocked the effect of midazolam on total number of licks by selectively attenuating mean bout duration. Midazolam also produced a significant decrease in the intrabout lick rate, probably due to the muscle relaxant effects of this drug. This decrease in the intrabout lick rate was reversed by pretreatment with flumazenil but not by naloxone. The results suggest that endogenous opioids may be important for the palatability effects of midazolam, but may not be involved in the muscle relaxant effects of this drug.

Animals↗
PubMed1997

Devazepide attenuates dl-fenfluramine-induced suppression of gastric emptying but not food intake in the 17 h food-deprived rat.

Recently a number of studies have provided evidence which suggests that CCK and 5-HT interact in the control of food intake. The present experiments further examine this mechanism and the possibility that CCK and 5-HT interact in the control of gastric emptying. The selective CCK-A receptor antagonist, devazepide, (0.03-3.0 mg/kg) administered alone had no intrinsic effect on gastric emptying. Devazepide (0.1 and 0.3 mg/kg) blocked dl-fenfluramine-induced (3.0 mg/kg) suppression of gastric emptying. However, devazepide (0.03-3.0 mg/kg) failed to attenuate the anorectic effect of the same dose of dl-fenfluramine. These results suggest that under the present experimental conditions CCK and 5-HT interact in the regulation of gastric emptying but not food intake. Thus the interaction between CCK and 5-HT in the regulation of gastric emptying appears not to affect the control of ingestive behaviour.

Animals↗
PubMed1997

Autoradiographic mapping of brain 5-HT2A binding sites in P and in AA alcohol-preferring rats.

There is considerable evidence for an involvement of serotonergic mechanisms in the control of alcohol consumption. In the present study, an extensive 5-HT2A receptor autoradiographic investigation was carried out in two genetically selected rat strains, P and AA alcohol-preferring rats, respectively, as well as in the corresponding NP and ANA alcohol-nonpreferring rats. The aim was to determine if there is any common pattern in 5-HT2A binding site densities that may illuminate mechanisms of alcohol preference in these animals. For quantitating 5-HT2A binding sites, [3H]ketanserin (2 nM) was used. Nonspecific binding was measured in the presence of methysergide 10(-6) M. Results demonstrated a lower level (from 50 to 70%) of 5-HT2A binding sites in the layer IV of prefrontal cortex, frontal cortex, parietal cortex of P rats compared to NP controls. Similarly, in the claustrum, 5-HT2A binding density of P rats was 50% lower than that of NP rats, although this failed to achieve statistical significance. No difference was detected in the other areas investigated, including the olfactory tubercles, nucleus accumbens, caudate putamen, pyriform cortex, ventral tegmental area, temporal cortex, and entorhinal cortex. In AA rats, [3H]ketanserin binding density measured in these brain areas was very similar to that observed in ANA nonpreferring controls, and statistical analysis did not reveal any significant difference between the two rat lines. The present study confirms previous reports demonstrating lower densities of 5-HT2A binding sites in the P rats and provides the first autoradiographic evidence showing that such an alteration does not occur in AA rats. These findings suggest that the expression of high alcohol preference in genetically selected P and AA rats is not associated with a shared neurochemical alteration of the 5-HT2A receptor system.

Alcoholism↗
PubMed1997

Effects of amino acid side-chain volume on chain packing in genetically engineered periodic polypeptides.

The fidelity of bacterial protein synthesis allows the production of architecturally well-defined polymeric materials through precise control of chain length, sequence, stereochemistry, and interchain interactions. In the present paper, we examine the relation between amino acid residue volume and crystalline unit cell dimensions, in a set of periodic protein polymers of repeating unit sequence -(AlaGly)3-X-Gly-, where X is Asn, Phe, Ser, Val, or Tyr. The proteins were overexpressed in Escherichia coli, purified by simple procedures based on acid/ethanol precipitation or insolubility in aqueous sodium dodecyl sulfate, and processed to form oriented crystalline mats by precipitation from formic acid under mechanical shear. X-ray diffraction analyses revealed that the basic structures of the -(AlaGly)3-X-Gly- polymers are identical to that previously reported for [(AlaGly)3-GluGly]36, [Krejchi, M.T., Atkins, E.D.T., Waddon, A.J., Fournier, M.J., Mason, T.L., and Tirrell, D.A. (1994) Science 265, 1427-1432], with the oligoalanylglycine segments forming antiparallel beta-sheets and the substituted amino acids occurring within three-residue folds at the lamellar surfaces. The X-ray diffraction signals for each member of the family index on an orthorhombic unit cell; the a-axis (hydrogen bond direction) and c-axis (chain direction) spacings remain invariant but the b-axis (sheet stacking direction) spacing increases with increasing volume of the substituted amino acid. The results obtained from a variant with alternating Glu and Lys substitution at the X position, together with the results previously reported for poly(L-alanylglycine) [Panitch, A., Matsuki, K., Cantor, E.J., Cooper, S.J., Atkins, E.D.T., Fournier, M.J., Mason, T.L., and Tirrell, D.A. (1997) Macromolecules 30, 42-49] are included for comparison. The average intersheet stacking distance (b/2) increases linearly with the volume of the amino acid inserted at position X. Because the chain-folded lamellar architecture adopted by these periodic polypeptides accommodates a wide range of residues differing in charge, steric bulk, and hydrophobicity, these results illustrate a new approach to the engineering of intermolecular interactions in polymeric solids.

Amino Acids↗
PubMed1997

Plasma noradrenaline response to electroconvulsive therapy in depressive illness.

BACKGROUND: Abnormalities of catecholaminergic function have been hypothesised to cause depressive illness. Plasma noradrenaline can be used as a marker of central noradrenergic activity. It is of interest to examine the change in resting plasma noradrenaline in patients with depressive illness over a course of electroconvulsive therapy (ECT) and relate this to their clinical state. METHOD: Patients referred for ECT who suffered from DSM-III-R major depressive disorder or dysthymia were recruited. Blood samples were taken before and after each treatment, during a course of ECT, to measure plasma noradrenaline and cortisol. Clinical ratings were carried out weekly during the course of ECT. RESULTS: Plasma noradrenaline fell significantly in those patients with melancholic/psychotic depressions but increased in those with non-melancholic depressive illness. There was a strong trend indicating that a fall in plasma noradrenaline was associated with improvement in depression ratings in the melancholic/psychotic patients only. CONCLUSIONS: Electroconvlusive therapy decreases plasma noradrenaline in melancholic/psychotic depressive illness and this shows a trend associated with clinical improvement.

Adult↗
PubMed1996

The crystal structure of a class II fructose-1,6-bisphosphate aldolase shows a novel binuclear metal-binding active site embedded in a familiar fold.

BACKGROUND: [corrected] Aldolases catalyze a variety of condensation and cleavage reactions, with exquisite control on the stereochemistry. These enzymes, therefore, are attractive catalysts for synthetic chemistry. There are two classes of aldolase: class I aldolases utilize Schiff base formation with an active-site lysine whilst class II enzymes require a divalent metal ion, in particular zinc. Fructose-1,6-bisphosphate aldolase (FBP-aldolase) is used in gluconeogenesis and glycolysis; the enzyme controls the condensation of dihydroxyacetone phosphate with glyceraldehyde-3-phosphate to yield fructose-1,6-bisphosphate. Structures are available for class I FBP-aldolases but there is a paucity of detail on the class II enzymes. Characterization is sought to enable a dissection of structure/activity relationships which may assist the construction of designed aldolases for use as biocatalysts in synthetic chemistry. RESULTS: The structure of the dimeric class II FBP-aldolase from Escherichia coli has been determined using data to 2.5 A resolution. The asymmetric unit is one subunit which presents a familiar fold, the (alpha/beta)8 barrel. The active centre, at the C-terminal end of the barrel, contains a novel bimetallic-binding site with two metal ions 6.2 A apart. One ion, the identity of which is not certain, is buried and may play a structural or activating role. The other metal ion is zinc and is positioned at the surface of the barrel to participate in catalysis. CONCLUSIONS: Comparison of the structure with a class II fuculose aldolase suggests that these enzymes may share a common mechanism. Nevertheless, the class II enzymes should be subdivided into two categories on consideration of subunit size and fold, quaternary structure and metal-ion binding sites.

Amino Acid Sequence↗